第十一届北京罕见病学术大会暨2023京津冀罕见病学术大会征文(097)

1Department of Neurology， Peking University First Hospital

2Beijing Key Laboratory of Neurovascular Disease Discovery

3Key Laboratory of for Neuroscience， National Health Commission of the People’s Republic of China， Peking University

Yikang Wang^1†， Meng Yu^1†， Yawen Zhao¹， Zheng Yiming¹， Jing Liu¹， Qingqing Wang¹，

 Wei Zhang^1，2， Zhaoxia Wang^1，2， Jianwen Deng^1，2， Yun Yuan^1，2，3*

Dyspherlinopathy is an autosomal recessive muscular dystrophy related to dyspherlin gene mutations. The main pathological changes is characterized by myofiber necrosis with macrophage infiltration with absence of dyspherlin. Our aim was to investigate the recruitment and polarization of macrophages in dyspherlinopathy.

Methods：We collected 12 patients of dyspherlinopathy. Immunofluorescence was applied to determine M2 marophages and satellite cells of muscle fibers. RNA-seq and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of skeletal muscle tissue carried out to explore macrophage polarization pathway. Quantibody® Human Inflammation Array 3 was used to assay serum macrophage related cytokines/chemokines.

Results：Immunofluorescence showed M2 macrophages in skeletal muscles of dysferlinopathy. KEGG analyses showed upregulation of PI3K-Akt signaling pathway. The number of M2 macrophages in the muscle was positively correlated with the number of satellite cells and necrotic myofibers. Serum macrophage related CCL4 were significantly higher in dysferlinopathy (P = 0.002).

Conclusion：M1/M2 macrophage balance polarization governs the development of dyspherlinopathy， which depend on PI3K-Akt pathway.